The main purpose of this proposed research is to understand the structure-function relationships in biological membranes, in particular the relationship between membrane transport and its molecular structure. We have chosen bacterial membranes as models for biological membranes. Our basic experimental approach is to combine chemical, genetic, and physical techniques to investigate membrane transport. Chemical techniques are needed to synthesize a number of fluorinated and deuterated fatty acid and amino acid analogs to be biosynthetically incorporated into phospholipids and membrane proteins as NMR probes. Genetic techniques are needed to isolate appropriate auxotrophs for the incorporation of these NMR probes into phospholipids and binding proteins and to isolate suitable mutants for reconstituting membranes from components. 1H, 2H, and 19F NMR techniques will be used to detect conformational changes in the fluorine and deuteium labeled binding proteins and phospholipids in membranes during the transport process. We shall study the properties of the binding proteins, phospholipids, model membranes, and reconstituted membranes in relation to membrane transport. It is expected that one of the important developments in biomedical sciences during the next few years will center on explaining the roles of membranes in living cells and on explaining the structure-function relationships of "altered" membranes in malignant cells (such as cancer cells). We hope that the results obtained from this proposed research will contribute to an understanding of some of the essential cellular processes not only in bacterial cells but also in mammalian cells.